Current knowledge concerning the central nervous system neuropathways and neurotransmitters controlling respiration is incomplete. We have been using neuroanatomical and neuropharmacological techniques in order to extend our knowledge in this area and found that stimulation of the caudal raphe nuclei produces changes in respiratory motor outflow of the phrenic and recurrent laryngeal nerves that are mediated by serotonergic neuropathways. The overall objective of this proposal is to investigate the role of the serotonergic neurons of the caudal raphe nuclei in respiratory control in the cat. The specific aims are to: 1) Identify the connections of the caudal raphe nuclei with other established respiratory nuclei including the dorsal respiratory group, ventral respiratory group, Botzinger Complex, pontine respiratory group and recurrent laryngeal nerve motoneurons of the nucleus ambiguus; 2) Determine if serotonin is a neurotransmitter used by caudal raphe projections to these respiratory nuclei; 3) Determine if serotonin innervates functionally identified respiratory neurons in these respiratory nuclei; and 4) Determine the involvement of serotonin in mediating the changes in phrenic nerve and recurrent laryngeal nerve activity evoked by stimulation of the caudal raphe nuclei. Methods to be used include: anterograde tracing with lectin, retrograde tracing with fluorescent dyes, immunohistochemistry, phrenic nerve recording, recurrent laryngeal nerve recording, electrical and chemical (L-glutamate) stimulation of brain nuclei, extracellular recording of respiratory neuron activity, and pressure microinjection of drugs affecting serotonergic activity. There is a critical need for further basic research to define the synaptic relationships and neurotransmitters of central respiratory neurons. This research is of clinical importance also as increased knowledge of the neurochemical basis of respiratory control will increase the possibilities of improving pharmacological intervention in respiratory disorders including sleep apnea, sudden infant syndrome and the chronic obstructive pulmonary diseases.